Field of the Invention
The present disclosure relates to diagnose of liver cancer based on the immunological detection of biomarker.
Description of the Related Art
Hepatic disease is one of the most prevalent disorders in human and there are over 100 known forms, many of which are fatal. Particularly Hepatocellular carcinoma (HCC) is the 5th leading cause of cancer related death worldwide and the death rate due to HCC is on the rise. Patients with HCC are usually asymptomatic until the later stage. Therefore, the patients can be greatly benefited by early diagnosis or detection.
Several parameters are currently used to examine the proper function of liver in clinical practice. One of them is to measure the level of Aspartate aminotransferase (AST), which is found in high concentration in hepatocytes. AST is released from hepatocytes into the blood when hepatocytes are damaged due to various factors such as toxic materials, viral infection, excess alcohol intake, and obesity. AST catalyzes reversible reactions of converting L-aspartate and α-ketoglutarate to oxaloacetate and L-glutamate, respectively and thus are used to diagnose and monitor liver disease, particularly the one resulting in a destruction of hepatocytes.
AST exists in mammalian tissues as two distinct isoenzymes, one located in the cytoplasm (cAST), and the other in mitochondria (mAST). Although there have been serval attempts, the measurement of isoenzymes has not been widely utilized for clinical diagnosis of hepatic disease. This is due to the pyridoxal-5-phosphate (co-enzyme of AST) that negatively affects the measurement leading to the inaccurate results. A typical use of AST in connection with liver disease is to measure the total enzymatic activities of both cAST and mAST. However, the test results may not represent the exact amount of AST present in tissues since they may be degraded or modified in the blood stream after they have been released into the blood.
According to the previous studies, liver, heart, skeletal muscle, kidneys, and brain are the main sources of AST and did not disclose regarding the separate distribution or presence of cAST and mAST.
KR Patent Publication No. 2002-0053113 relates to an immunological method of quantitative measurement of enzymes in serum such as AST. However, there are no mention in relation to the separate measurement of cAST and mAST for diagnosis of liver disease.
U.S. Pat. No. 7,981,627 relates to a method of monitoring and diagnosing liver cirrhosis including measuring AST level in the blood of a subject.
US Patent Publication No. 2006-0172286 relates to a method of diagnosing liver cancer including determining the activity of biomarker such as AST in the serum or blood of a subject.
However, they do not disclose measuring the cytoplasmic and mitochondrial isoforms of AST separately in connection with diagnosis of liver disease.